Our goal is the improved diagnosis and treatment of patients with hemostatic defects, and so we have been studying normal and abnormal hemostasis. The interaction of the platelet and the blood vessel is being investigated in pigs with von Willebrand's disease. The production of von Willebrand factor and its interaction with the platelet is being studied in endothelial cell cultures. The structure and function of purified von Willebrand factor is being investigated and the role of this material in hemostasis by in vivo and in vitro techniques including interaction of platelets with artificial surfaces. The investigation of the Willebrand factor molecule is being extended by attempts to purify and characterize factor VIII coagulant activity. Pigs with von Willebrand's disease appear to be resistant to the development of atherosclerosis, and the role of the platelet in atherosclerosis is being investigated. The platelet is also being studied as the initiator of intrinsic coagulation. Normal coagulation involves the activation of prothrombin which is being studied in purified systems and by measuring the turnover of the activation products in dogs. Immunologic probes are being used to investigate the activation products of prothrombin (including thrombin) and other coagulation factors such as factor V. In conjunction with the platelet studies, the regulation of coagulation by circulating inhibitors is being investigated including the role of platelet factor 4 and heparin. The investigation of normal and abnormal hemostasis is designed to give greater insight into the normal control of hemostasis and how symptoms arise and laboratory tests become abnormal when the control is imperfect.